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排序方式: 共有710条查询结果,搜索用时 15 毫秒
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Dam J Guan R Natarajan K Dimasi N Chlewicki LK Kranz DM Schuck P Margulies DH Mariuzza RA 《Nature immunology》2003,4(12):1213-1222
The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes. 相似文献
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Dahl N; Pigg M; Ristoff E; Gali R; Carlsson B; Mannervik B; Larsson A; Board P 《Human molecular genetics》1997,6(7):1147-1152
Severe glutathione synthetase (GS) deficiency is a rare genetic disorder
with neonatal onset. The enzymatic block of the gamma-glutamyl cycle leads
to a generalized glutathione deficiency. Clinically affected patients
present with severe metabolic acidosis, 5- oxoprolinuria, increased rate of
hemolysis and defective function of the central nervous system. The
disorder is inherited in an autosomal recessive mode and, until recently,
the molecular basis has remained unknown. We have sequenced 18 GS alleles
associated with enzyme deficiency and we detected missense mutations by
direct sequencing of cDNAs and genomic DNA. In total, 13 different
mutations were identified. Four patients were found to be compound
heterozygotes and two individuals were apparently homozygous. Reduced
enzymatic activities were demonstrated in recombinant protein expressed
from cDNAs in four cases with different missense mutations. The results
from biochemical analysis of patient specimens, supported by the properties
of the expressed mutant proteins, indicate that a residual activity is
present in affected individuals. Our results suggest that complete loss of
function of both GS alleles is probably lethal. It is postulated that
missense mutations will account for the phenotype in the majority of
patients with severe GS deficiency.
相似文献
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Mario Cocco Cristiana Bellan Roxane Tussiwand Davide Corti Elisabetta Traggiai Stefano Lazzi Susanna Mannucci Lucio Bronz Nazzareno Palummo Chiara Ginanneschi Piero Tosi Antonio Lanzavecchia Markus G. Manz Lorenzo Leoncini 《The American journal of pathology》2008,173(5):1369-1378
Recent studies suggest that Epstein-Barr virus (EBV) can infect naïve B cells, driving them to differentiate into resting memory B cells via the germinal center reaction. This hypothesis has been inferred from parallels with the biology of normal B cells but has never been proven experimentally. Rag2−/− γc−/− mice that were transplanted with human CD34+ cord blood cells as newborns were recently shown to develop human B, T, and dendritic cells, constituting lymphoid organs in situ. Here we used this model to better define the strategy of EBV infection of human B cells in vivo and to compare this model system with different conditions of EBV infection in humans. Our results support the model of EBV persistence in vivo in cases that were characterized by follicular hyperplasia and a relatively normal CD4+ and CD8+ T-cell distribution. Intriguingly, in cases that were characterized by nodular and diffuse proliferation with a preponderance of CD8+ T cells, similar to infectious mononucleosis, EBV still infects naïve B cells but also induces clonal expansion and ongoing somatic mutations without germinal center reactions. Our results reveal different strategies of EBV infection in B cells that possibly result from variations in the host immune response. Future experiments might allow understanding of the mechanisms responsible for persistent EBV infection and provide targets for more highly tailored therapeutic interventions. 相似文献
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Celiac disease (CD) is a chronic disease treated by maintaining and managing a lifelong restrictive gluten-free diet. The purpose of this study was to develop a mobile application, Plan My C-Day, to promote self-management skills among youth with CD during adolescence—a time when decreased adherence often occurs—and examine its usability among adolescents with CD. Plan My C-Day contains three simulations of activities involving eating out and actions to take when preparing for these events. It was developed and pilot tested by 13 adolescents with CD. Application use and user perception data were collected and analyzed. Participants chose 160 actions within the simulations. For over 75% of participants, the time to complete the simulation decreased from the first to the third (last) simulation by an average of 50%. The average reported usability perception was 3.71 on a scale of 1 to 5, with system ease of use and ease of learning obtaining the highest scores. This study demonstrated that the Plan My C-Day mobile application’s self-management content, features, and functions operated well and that the simulations were easy to understand and complete. Further development will include the option to add self-created activities and adaptation to different languages and cultures. 相似文献
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Ivan Galić Marin Vodanović Stipan Janković Frane Mihanović Enita Nakaš Samir Prohić Elizabeta Galić Hrvoje Brkić 《Journal of Forensic and Legal Medicine》2013,20(1):40-45
BackgroundDental age estimation in children plays an important role in forensic dentistry. The most commonly used method for age estimation was developed by Demirjian in 1973 on a French–Canadian sample. It generally overestimates dental age in many populations. International maturity standards were formed to obtain a predicted age with more confidence when ethnic origin was not available.ObjectivesThe aim of this study was to evaluate the applicability of Chaillet's international scores in the dental age assessment on Bosnian Herzegovinian (BH) children.MethodsOrthopantomograms of 1772 children, 980 girls and 792 boys aged 6.04–14.90 years, were assessed using Chaillet's international maturity tables and curves. The dental ages for both genders were compared to the chronological ages through a paired t-test.ResultsMean overestimation using Chaillet's international maturity standards were 0.09 ± 0.83 for girls and 0.28 ± 0.90 for boys. The absolute accuracy of residuals between the dental and chronological age were 0.65 ± 0.52 years for girls (Median: 0.52 years) and 0.73 ± 0.60 years for boys (Median: 0.57 years).ConclusionThe Polynomial compound formula was recommended to predict dental age with more accuracy for results of international maturity standards on BH children. 相似文献
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Sabina Gallati Simone Hess Dorothea Galié-Wunder Elisabeth Berger-Menz Dominik Böhlen 《Reproductive biomedicine online》2009,18(5):685-694
The objective of this study was to investigate the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) to human infertility and to define screening and counselling procedures for couples asking for assisted reproduction treatment. Extended CFTR mutation screening was performed in 310 infertile men (25 with congenital absence of the vas deferens (CAVD), 116 with non-CAVD azoospermia, 169 with severe oligospermia), 70 female partners and 96 healthy controls. CFTR mutations were detected in the majority (68%) of CAVD patients and in significant proportions in azoospermic (31%) and oligospermic (22%) men. Carrier frequency among partners of infertile men was 16/70, exceeding that of controls (6/96) significantly (P = 0.0005). Thus, in 23% of infertile couples both partners were carriers, increasing the risk for their offspring to inherit two mutations to 25% or 50%. This study emphasizes the necessity to offer extended CFTR mutation screening and counselling not only to patients with CAVD but also to azoospermic and oligozoospermic men and their partners before undergoing assisted reproduction techniques. The identification of rare and/or mild mutations will not be a reason to abstain from parenthood, but will allow adequate treatment in children at risk for atypical or mild cystic fibrosis as soon as they develop any symptoms. 相似文献